The long term objectives of the proposed research are to elucidate the roles of the forebrain in the control of effector systems in the central nervous system of mammals. Chemically-defined pathways originating in the forebrain and terminating in neuroendocrine, autonomic and classical motor areas will be studied with combined morphological and immunohistochemical techniques. Twelve groups of experiments are designed to address three specific aims. The first specific aim addresses the hypothesis that the forebrain extrapyramidal motor systems control the neuroendocrine, autonomic and classical motor systems, in part, through the mesopontine tegmentum. Combined retrograde and anterograde tracing techniques are applied at the light and electron microscopic levels to determine if neurons in the mesopontine tegmentum which project to the hypothalamus, brainstem and spinal cord receive input from pallidal and peripallidal neurons of the forebrain motor and limbic systems. The second specific aim addresses the hypothesis that the mesopontine tegmental area which receives convergent forebrain inputs contains separate sets of transmitter-specific neurons which have stereospecific projections to neuroendocrine, autonomic, and classical motor areas. Multiple labeling immunohistochemical techniques are combined with retrograde tracing techniques to determine the neurochemical content and axon collateralization patterns of mesopontine projections to the hypothalamus, brainstem and spinal cord. The third specific aim addresses the hypothesis that the traditional hypophysiotrophic zones contain two functional types of neurons: one which controls the pituitary and a second which projects back to higher forebrain areas. Combined tract tracing and immunocytochemical techniques used at the light and electron microscopic levels will be used to determine both the chemistry and connections of different sets of defined hypothalamic neuronal systems. The proposed studies will enhance our understanding of the higher neuronal control of motor systems and will provide new information on how the forebrain, brainstem and hypothalamus integrate diverse motor systems in humans.